Intervention treatment, in which a balloon or a stent is inserted into a blood vessel, and a narrowed portion is spread therewith, has been conventionally carried out for patients with ischemic heart diseases having a narrowed coronary artery due to arterial sclerosis or thrombus formation.
In this process, rubbing by the balloon or the stent may occur in the narrowed portion to cause detachment of vascular endothelial cells, causing injury of the portion. As a result, inflammation of the blood vessel, intimal hyperplasia due to abnormal growth of smooth muscle cells or cardiac muscle cells behind the endothelial cells at the injured site, or another thrombus formation, may occur to narrow the blood vessel again. Thus, a coil to which a sustained-release formulation of a drug for preventing inflammation, hypertrophy, or thrombosis is applied needs to be inserted into this site to prevent the restenosis and the like. This treatment is laborious, and imposes a heavy burden on the patient.
Fibrous disorders, such as those in which excessive fibrosis causes pathological disorders and tissue dysfunctions, are caused by abnormal accumulation of a fibrous tissue in a tissue. This fibrous tissue is generated also by disorder processes other than surgery, injury, and wounding, and examples of such processes include chronic disorders such as liver cirrhosis, hepatic fibrosis, glomerulonephritis, pulmonary fibrosis, scleroderma, myocardial fibrosis, fibrosis after myocardial infarction, central nervous system fibrosis after an attack or a neurodegenerative disorder (for example, Alzheimer's disease), proliferative vitreoretinopathy (PVR), restenosis (after, for example, angioplasty), and arthritides.
A simple system which enables specific delivery of these drugs to the heart, a blood vessel, or a site injured by fibrosis, for treatment of (that is, suppression or prevention of or recovery from) the symptoms described above has been demanded. As drug delivery systems, Non-patent Document 1 describes a complex of neoglycoprotein and liposome as a sugar chain-introduced drug delivery material, and Non-patent Document 2 describes a complex of polyethyleneimine and arabinogalactan, which is a gene delivery agent specific to hepatocytes. However, these do not have specific affinity to injured sites of the heart or blood vessels.
Use of a convertase inhibitor in production of pharmaceuticals for reducing cicatrization during wound healing, or for reducing fibrosis during treatment of fibrotic conditions, which convertase inhibitor is to be topically applied to the site of injury or fibrotic disorder, has been proposed (see Patent Document 1). In terms of drug delivery agents and the like, drug delivery agents on which a compound showing specific interaction with a particular protein such as vimentin or desmin present in cardiac muscle cells, vascular smooth muscle cells, skeletal myoblasts, and/or the like damaged by ischemia or the like, for example, N-acetylglucosamine, is exposed, and drug delivery agents in which N-acetylglucosamine is bound to the surface of colloid particles through avidins with which the surface is coated (see Patent Documents 2 and 3), have been proposed. A drug delivery system and the like using a drug delivery carrier compound having a first region having affinity to lipid membrane containing a drug therein, and a second region which binds to the first region and contains an automagnetic organic molecule (see Patent Document 4), have also been proposed.